Overview

Phenylketonuria (fen-ul-key-toe-NU-ree-uh), also called PKU, is a rare inherited disorder that causes an amino acid called phenylalanine to build up in the body. PKU is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine.

Without the enzyme necessary to process phenylalanine, a dangerous buildup can develop when a person with PKU eats foods that contain protein or eats aspartame, an artificial sweetener. This can eventually lead to serious health problems.

For the rest of their lives, people with PKU — babies, children and adults — need to follow a diet that limits phenylalanine, which is found mostly in foods that contain protein.

Babies in the United States and many other countries are screened for PKU soon after birth. Recognizing PKU right away can help prevent major health problems.

Symptoms

Newborns with PKU initially don't have any symptoms. However, without treatment, babies usually develop signs of PKU within a few months.

PKU signs and symptoms can be mild or severe and may include:

A musty odor in the breath, skin or urine, caused by too much phenylalanine in the body

Neurological problems that may include seizures

Skin rashes (eczema)

Fair skin and blue eyes, because phenylalanine can't transform into melanin — the pigment responsible for hair and skin tone

Abnormally small head (microcephaly)

Hyperactivity

Intellectual disability

Delayed development

Behavioral, emotional and social problems

Psychiatric disorders

Severity varies

The severity of PKU depends on the type.

Classic PKU. The most severe form of the disorder is called classic PKU. The enzyme needed to convert phenylalanine is missing or severely reduced, resulting in high levels of phenylalanine and severe brain damage.

Less severe forms of PKU. In mild or moderate forms, the enzyme retains some function, so phenylalanine levels are not as high, resulting in a smaller risk of significant brain damage.

But most children with the disorder still require a special PKU diet to prevent intellectual disability and other complications.

Pregnancy and PKU

Women who have PKU and become pregnant are at risk of another form of the condition called maternal PKU. If women don't follow the special PKU diet before and during pregnancy, blood phenylalanine levels can become high and harm the developing fetus or cause a miscarriage.

Even women with less severe forms of PKU may place their unborn children at risk by not following the PKU diet.

Babies born to mothers with high phenylalanine levels don't often inherit PKU. But they can have serious consequences if the level of phenylalanine is high in the mother's blood during pregnancy. Complications at birth may include:

Low birth weight

Delayed development

Facial abnormalities

Abnormally small head

Heart defects and other heart problems

Intellectual disability

Behavioral problems

When to see a doctor

Seek medical advice in these situations:

Newborns. If routine newborn screening tests show that your baby may have PKU, your child's doctor will want to start dietary treatment right away to prevent long-term problems.

Women of childbearing years. It's especially important for women with a history of PKU to see a doctor and maintain the PKU diet before becoming pregnant and during pregnancy to reduce the risk of high blood phenylalanine levels harming their unborn babies.

Adults. People with PKU continue to receive care across the life span. Adults with PKU who have stopped the PKU diet in their teens may benefit from a visit with their doctors. Returning to the diet may improve mental functioning and behavior and slow damage to the central nervous system that can result from high phenylalanine levels.

Causes

Autosomal recessive inheritance pattern

Autosomal recessive inheritance pattern

To have an autosomal recessive disorder, you inherit two mutated genes, one from each parent. These disorders are usually passed on by two carriers. Their health is rarely affected, but they have one mutated gene (recessive gene) and one normal gene (dominant gene) for the condition. With each pregnancy, two carriers have a 25 percent chance of having an unaffected child with two normal genes (left), a 50 percent chance of having an unaffected child who is also a carrier (middle), and a 25 percent chance of having an affected child with two recessive genes (right).

A defective gene (genetic mutation) causes PKU, which can be mild, moderate or severe. In a person with PKU, this defective gene causes a lack of or deficiency of the enzyme that's needed to process phenylalanine, an amino acid.

A dangerous buildup of phenylalanine can develop when a person with PKU eats protein-rich foods, such as milk, cheese, nuts or meat, and even grains such as bread and pasta, or eats aspartame, an artificial sweetener. This buildup of phenylalanine results in damage to nerve cells in the brain.

Inheritance

For a child to inherit PKU, both the mother and father must have and pass on the defective gene. This pattern of inheritance is called autosomal recessive.

It's possible for a parent to be a carrier — to have the defective gene that causes PKU, but not have the disease. If only one parent has the defective gene, there's no risk of passing PKU to a child, but it's possible for the child to be a carrier.

Most often, PKU is passed to children by two parents who are carriers of the disorder, but don't know it.

Risk factors

Risk factors for inheriting PKU include:

Having both parents with a defective gene that causes PKU. Two parents must pass along a copy of the defective gene for their child to develop the condition.

Being of certain ethnic descent. The gene defect that causes PKU varies by ethnic groups and it's less common in African-Americans than in other ethnic groups.

Complications

Untreated PKU can lead to complications in infants, children and adults with the disorder. When mothers with PKU have high blood phenylalanine levels during pregnancy, fetal birth defects or miscarriage can occur.

Untreated PKU can lead to:

Irreversible brain damage and marked intellectual disability beginning within the first few months of life

Neurological problems such as seizures and tremors

Behavioral, emotional and social problems in older children and adults

Major health and developmental problems

Prevention

If you have PKU and are considering getting pregnant:

Follow a low-phenylalanine diet. Women with PKU can prevent birth defects by sticking to or returning to a low-phenylalanine diet before becoming pregnant. If you have PKU, talk to your doctor before you start trying to conceive.

Consider genetic counseling. If you have PKU, a close relative with PKU or a child with PKU, you may also benefit from genetic counseling before becoming pregnant. A doctor who specializes in medical genetics (geneticist) can help you better understand how PKU is passed through your family tree. He or she can also help determine your risk of having a child with PKU and assist with family planning.

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